Structure and localization of the human gene encoding SR-BI/CLA-1 - Evidence for transcriptional control by steroidogenic factor 1
Structure and localization of the human gene encoding SR-BI/CLA-1 - Evidence for transcriptional control by steroidogenic factor 1
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DOI：
10.1074/jbc.272.52.33068
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发表时间：
1997-12-26
影响因子：
4.8
通讯作者：
Hobbs, HH
中科院分区：
文献类型：
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作者：
Cao, GP;Garcia, CK;Hobbs, HH
清道夫受体，B类，1型受体（SR-BI）介导脂质从高密度脂蛋白到细胞的选择性转运。我们描述了人类SR-BI的结构和亚染色体定位，并提供证据表明它是由转录因子类固醇生成因子1（SF-1）调节的。SR-BI位于染色体12q24.2-qter上，跨越类似于75个内切酶对，并且包含13个外显子。人类组织的RNA印迹分析揭示了与先前描述的啮齿动物相似的表达模式，在肾上腺、卵巢和肝脏中mRNA水平最高。与啮齿类动物不同，人SR-BI在胎盘中以高水平表达。对SR-BI的转录起始位点进行了定位，DNA序列分析显示在近端5 '侧翼序列中存在SF-1的结合位点。SF-1是核激素受体基因家族的孤儿成员，在类固醇生成的调节中起关键作用，并且在类固醇生成组织中以高水平表达。SF-1以序列特异性方式结合SR-BI启动子，并且在肾上腺皮质Y1细胞中从该启动子的有效转录依赖于完整的SF-1位点。这些数据扩展了我们对类固醇生成组织内SF-1功能的理解，并表明SR-BI是参与类固醇生成的SF-1响应基因库的一部分，SR-BI用于为选定的组织提供脂蛋白衍生的脂质。
The scavenger receptor, class B, type 1 receptor (SR-BI) mediates the selective transport of lipids from high density lipoprotein to cells. We describe the structure and subchromosomal location of human SR-BI and provide evidence that it is regulated by the transcription factor, steroidogenic factor 1 (SF-1). SR-BI resides on chromosome 12q24.2-qter, spans similar to 75 kilobase pairs, and contains 13 exons. RNA blot analysis of human tissues reveals an expression pattern similar to that described previously for rodents with the highest levels of mRNA in the adrenal gland, ovary, and liver. Unlike rodents, human SR-BI was expressed at high levels in the placenta. The transcription start site for SR-BI was mapped, and DNA sequence analysis revealed a binding site for SF-1 in the proximal 5'-flanking sequence. SF-1, an orphan member of the nuclear hormone receptor gene family, plays a key role in the regulation of steroidogenesis and is expressed at high levels in steroidogenic tissues. SF-1 binds to the SR-BI promoter in a sequence-specific manner, and efficient transcription from this promoter in adrenocortical Y1 cells is dependent on an intact SF-1 site. These data extend our understanding of SF-1 function within steroidogenic tissues and suggest that SR-BI, which serves to supply selected tissues with lipoprotein-derived lipids, is part of the repertoire of SF-1-responsive genes involved in steroidogenesis.